SUMMARY/ABSTRACT There are 16 million cancer survivors in the United States, and approximately 60% are age 65 years and over. By 2040, it is estimated that the number of cancer survivors will grow to 26 million with 73% age 65 and older and almost 50% age 75 and older. Despite this so-called silver tsunami of older cancer survivors, there are significant knowledge gaps regarding how cancer and cancer treatment impacts the aging process. There is also a growing consensus regarding the need for studies of cancer in older adults because of the prevalence of comorbidities, functional losses, cognitive impairment, and frailty, and particularly for those age ? 75 for whom there are virtually no data. Studies are needed to better understand how cancer and its treatment interact with underlying vulnerabilities, which in turn impacts the feasibility, safety, and efficacy of interventions in this population. The Life and Longevity After Cancer (LILAC) project is a cancer survivor cohort embedded within the Women?s Health Initiative to support studies of cancer survivorship in an aging population. During the initial funding period, we developed the LILAC cohort of 13,453 WHI cancer survivors who were diagnosed with one of eight LILAC designated cancers: invasive breast, colorectal, endometrial, melanoma, leukemia, lung, lymphoma, melanoma, or ovarian. We collected information on first course of treatment, clinical and patient reported outcomes, as well as archival tissue from 4351 solid tumors. With a minimum of 20 years of data on these women and a current age-range of 70 to101 years, the LILAC population is poised to provide key information on cancer and aging to advance our cancer and aging research agenda. To accomplish this we propose to enhance the LILAC resource through several mechanisms designed to support analyses of emerging questions. Specifically, we propose: 1) To fill critical gaps in knowledge regarding the self-reported physical, mental and social health of older female cancer survivors by continuing to enroll newly diagnosed survivors (N=2685) and follow the LILAC cohort; 2) To develop the analytic framework to assess trajectories of aging, including an accelerated aging phenotype in the WHI/LILAC database; 3) To establish cohorts of age- matched WHI participants with similar data who have remained cancer free, to help us understand the diagnosis of cancer and its treatment on the trajectories of aging, the accelerated aging phenotype and age- related comorbidities; 4) To obtain performance-based measures of physical function and new post-treatment blood samples to assess potential biomarkers of accelerated aging; and 5) To maximize the use and impact of this resource. Given the aging of the US population, the increase in the number of cancer survivors and the association between cancer and aging, these strategic and timely investments in the LILAC infrastructure will help to fill many of these critical research gaps.